Elucidating the α-amylase inhibitory activity of phytochemicals from Artocarpus altilis: An in silico and in vitro approach

Diabetes mellitus is a metabolic disease that can be managed effectively by alpha-amylase inhibition. This study isolated phytochemicals from Artocarpus altilis and evaluated their alpha-amylase inhibitory potential using computational and in vitro approaches. Barks of A. altilis collected from the wild, were dried, pulverized, and macerated with 50 % EtOH. The extract was defatted and subsequently partitioned into CHCl3. The CHCl3 fraction was subjected to repetitive column chromatography over silica, and Sephadex purification to afford Compounds A1, A2, and A3 which were identified and elucidated using H-1 NMR, C-13 NMR, 2D-NMR, and HRESIMS spectroscopic techniques. The alpha-amylase inhibitory activity of isolated compounds was examined using molecular docking, molecular dynamics simulation, MMPBSA, ADMET and in vitro methods. Spectroscopic characterisation and elucidation identified Compounds A1, A2, and A3 as 6,7-(2,2-dimethylpyrano)-5,2'4',5'-tetrahydroxy-3-prenylflavone, 3-Hydroxycudraflavone and 6,7-(2,2-dimethylpyrano-3-dihydrogeranyl-2-hydroxyl-3-methyl-5,8-dimethoxyl-gamma-benzopyrone respectively. Molecular docking studies revealed that compound A2 exhibited the highest binding affinity (-8.8 kcal/mol) followed by A1 (-8.6 kcal/mol) and A3 (-8.4 kcal/mol), as against acarbose (-7.7 kcal/mol). The same result was replicated in the molecular dynamics simulation and MMPBSA analysis such that A2 gave better binding energy than A1, A3, and acarbose. Also, the ADMET study showed the phytochemicals possesses good drug-like properties. The in vitro alpha-amylase inhibitory activity showed that binding energies with alpha-amylase in the order A2 (IC50 of 0.030 mu M) > A1 (IC50 of 0.032 mu M) > A3 (IC50 of 0.045 mu M) as compared acarbose (0.049) mu M.